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Ovarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting.This review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting.Protein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.

OBJECTIVE To evaluate the impact of early treatment and IL1RN genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (JIA). METHODS Response to anakinra was defined as achievement of clinically inactive disease (CID) at 6 months without glucocorticoid treatment. Demographic, clinical, and laboratory characteristics of 56 patients were evaluated in univariate and multivariate analyses as predictors of response to treatment. Six single-nucleotide polymorphisms (SNPs) in the IL1RN gene, previously demonstrated to be associated with a poor response to anakinra, were genotyped by quantitative polymerase chain reaction (qPCR) or Sanger sequencing. Haplotype mapping was performed with Haploview software. IL1RN messenger RNA (mRNA) expression in whole blood from patients, prior to anakinra treatment initiation, was assessed by qPCR. RESULTS After 6 months of anakinra treatment, 73.2% of patients met the criteria for CID without receiving glucocorticoids. In the univariate analysis, the variable most strongly related to the response was disease duration from onset to initiation of anakinra treatment, with an optimal cutoff at 3 months (area under the curve 84.1%). Patients who started anakinra treatment ≥3 months after disease onset had an 8-fold higher risk of nonresponse at 6 months of treatment. We confirmed that the 6 IL1RN SNPs were inherited as a common haplotype. We found that homozygosity for ≥1 high-expression SNP correlated with higher IL1RN mRNA levels and was associated with a 6-fold higher risk of nonresponse, independent of disease duration. CONCLUSION Our findings on patients with systemic JIA confirm the important role of early interleukin-1 inhibition and suggest that genetic IL1RN variants predict nonresponse to therapy with anakinra.

OBJECTIVE Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Background Standard open techniques for pedicle screws placement require extensive tissue dissection for optimal screw trajectory. Furthermore, they have been associated with extensive blood loss, long hospital stays and, consequently, significant costs. Objective To describe a percutaneous pedicle screw fixation performed with a novel navigated “one-step” system, underlining the safety and effectiveness of such technique. Methods During a 43-month period, 43 patients with 230 pedicle screws were evaluated. Percutaneous pedicle screw fixation was performed in the lumbosacral region in 5 patients (12%), lumbar region in 13 (30%), thoraco-lumbar region in 21 (49%) and thoracic region in 4 (9%). We have compared the accuracy rates of screw placement achieved with percutaneous pedicle screw fixation using fluoroscopy, and neuronavigated percutaneous pedicle screw fixation using an innovative “one-step” technique. Results Statistical differences in screws placement accuracy between the group A and B were evaluated by Fisher exact test. The accuracy rate of pedicle screws placement in group with the intraoperative navigation system was higher than that of the group with fluoroscopy (P = 0.04). There was no hardware failure except 3 screws of Group A (1.3%) that pulled out few weeks after surgery, There were a total of 6 SAR (2.61%) and only 1 of them belonged to group B, without the need of revision surgery (0.61% out of the total neuronavigated stabilizations), while the other 5 represent 7.35% of the total screws placed with fluoroscopy. In our patient series the risk of mispositioning has been reduced by 14.95% with the use of the neuronavigation system, considering as malposition the set of IMP and SAR. Conclusions Percutaneous pedicle screw fixation with neuronavigated “one-step” technique represents a safe and effective tool in minimally invasive spine surgery that deserves a further investigation and widespread diffusion.

This study assesses the structural vulnerability of part of a later medieval earthen building at Ambel (near Zaragoza, Spain), once a preceptory or monastic house belonging to the Military Orders. An inspection of its morphology and materials coupled with the results of an extensive campaign of static monitoring reveals marked structural inhomogeneities, the product of more than a thousand years of construction, failure and repair from the 10th century to the present day. Building materials are inappropriately juxtaposed, there are discontinuities between construction phases and fundamental concerns remain over the long-term stability of the structure. The current condition of the structure is mainly influenced by structural discontinuities introduced at the time of construction, the unintended consequences of repair and modification and the material decay that has affected the base of the rammed earth walls. The overall findings of the static monitoring show that there is no related damage, variations in crack widths are related to the building seasonal cycle. While static analysis is an essential prerequisite before a suitable maintenance program can be fully defined, this study argues that no evaluation of the structural behaviour of any historic building can afford to ignore its archaeological ‘biography’ of modification and repair.

Das Wissen uber die Materialeigenschaften und die Versagensmechanismen bei Lehmbaustoffen ist begrenzt und luckenhaft. Im Rahmen des EU-Projekts NIKER (www.niker.eu) wurden deshalb die mechanischen Eigenschaften von Bauteilen aus Lehm unter statischer Druck- und Schubbeanspruchung bestimmt. Ziel der Untersuchungen war es, grundlegende Daten zum Verformungs- und Versagensverhalten von Lehmbauteilen zu erhalten und dieses mit einem numerischen Modell zu beschreiben. Die Versuchsergebnisse belegten das sprode Verhalten von Lehmsteinmauerwerk bei uniaxialer Druckbelastung und zeigten, dass das Versagen von Lehmsteinmauerwerk infolge Schubbelastung nach Erstrissbildung in Mortelfugen und Lehmsteinen durch Gleiten der Lehmsteine entlang der Mortelfugen erfolgt. Die numerische Makromodellierung erbrachte zwar befriedigende Resultate hinsichtlich des Spannungs-Dehnungs-Verhaltens, jedoch konnte bei der simulierten Rissbildung keine Ubereinstimmung mit den in den Versuchen beobachteten Rissbildern erzielt werden. Bei Lehmsteinmauerwerk ist also eine wesentlich aufwendigere Mikromodellierung notwendig, um das Versagensverhalten korrekt beschreiben zu konnen. Knowledge of the material properties and failure mechanisms of earthen materials is limited and scattered. Within the framework of the NIKER project (www.niker.eu) funded by EC, the mechanical properties of earthen material elements were therefore determined under static compression and shear loads. The aim was to obtain fundamental data on deformation behaviour and failure mechanisms of earthen material structural elements and to describe them by means of a numerical model. The test results confirmed the brittle behaviour of earth block masonry under monoaxial compressive load and showed that the failure of earth block masonry under shear load occurs by sliding of the earth blocks along the mortar joints after initial cracking in mortar joints and earth block. Numerical macro modelling showed satisfying results with regard to stress-strain behaviour, but the simulated crack pattern was not consistent with experimental observations. In the case of earth block masonry, it is thus necessary to use micro modelling approaches in order to correctly predict the failure process at local level.

The relationship between depression and dementia in the elderly has been widely investigated, but the real interplay between these variables is still not clear. This observational study highlights the influence of some basic variables, such as sex and age, in the development of dementia and major depression. It shows (i) the importance of sex in the age of onset of depression and dementia, (ii) the presence of two types of depressive syndrome, the first linked to the development of dementia, the second as reactive depression; (iii) the need for more attention to depressive symptoms in young-elderly men.

Motor resonance is defined as the subliminal activation of the motor system while observing actions performed by others. However, resonating with another person's actions is not always an appropriate response: In real life, people do not just imitate but rather respond in a suitable fashion. A growing body of neurophysiologic studies has demonstrated that motor resonance can be overridden by complementary motor responses (such as preparing a precision grip on a small object when seeing an open hand in sign of request). In this study, we investigated the relationship between congruent and incongruent corticospinal activations at the level of multiple effectors. The modulation of motor evoked potentials evoked by single-pulse TMS over the motor cortex was assessed in upper and lower limb muscles of participants observing a soccer player performing a penalty kick straight in their direction. Study results revealed a double dissociation: Seeing the soccer player kicking the ball triggered a motor resonance in the observer's lower limb, whereas the upper limb response afforded by the object was overridden. On the other hand, seeing the ball approaching the observers elicited a complementary motor activation in upper limbs while motor resonance in lower limbs disappeared. Control conditions showing lateral kicks, mimicked kicks, and a ball in penalty area were also included to test the motor coding of object affordances. Results point to a modulation of motor responses in different limbs over the course of action and in function of their relevance in different contexts. We contend that ecologically valid paradigms are now needed to shed light on the motor system functioning in complex forms of interaction.

The present paper describes the Epode Umbria Region Obesity Prevention Study (EUROBIS) and aims to implement the C.U.R.I.A.MO. model through the EPODE methodology. The main goal of the EUROBIS is to change the pendency of slope of the actual trend towards the increase in the yearly rates of childhood overweight and obesity in Umbria and to improve healthy lifestyles of children and their parents. The project is the first EPODE program to be performed in Italy. The aims of the Italian EUROBIS study are: (1) a community-based intervention program (CBP) carrying out activities in all primary schools of the Umbria Region and family settings as first step, to reverse the current obesity trend on a long-term basis, and (2) a clinical care program for childhood and adolescent by C.U.R.I.A.MO. model. C.U.R.I.A.MO. model is a multidisciplinary approach to improve three key aspects of healthy lifestyles: nutrition, exercise, and psychological aspects with the strategy of a family-based approach. The community-based intervention and clinical trial provide an innovative valuable model to address the childhood obesity prevention and treatment in Italy.

A rapid and specific diagnostic test for Alzheimer’s disease (AD), the prevalent cause of dementia in the elderly, is currently unavailable. The aim of this study was to verify the validity of the recently proposed ‘Eye Test’ in the identification of AD patients, based on their supposed greater mydriatic response to cholinergic antagonists. We tested the pupillary response to the instillation of 0.01% tropicamide in 48 subjects: 15 patients with probable or possible Alzheimer’s disease, five patients with vascular dementia (VD), 16 elderly controls (EC) and 12 young controls (YC). Mean pupil dilation in the treated eye at 30 and 40 min after drops instillation was not significantly different among the four groups. The mean change in anisocoria at 30 min was significantly greater in the AD group (0.90 mm, S.D. 0.83) than in the YC group (0.21 mm, S.D. 0.46), but no significant difference was found among the AD group, the EC group and the VD group. Our results, therefore, do not support the potential usefulness of the pupillary response to dilute tropicamide for identifying individuals with AD.

The analysis of variance for repeated measures was utilized, using the change of pupil diameter from baseline in the eye treated with tropicamide as a dependent variable. In a second analysis, we considered the change in anisocoria (difference between the change of pupil diameter in the treated eye and that in the contralateral eye) as a dependent variable, using the